Occupational exposure to manganese (Mn) occurs among workers involved in welding, smelting, mining, and battery production. In the US alone, millions of workers, including over 300,000 welders, are at high risk of excessive Mn exposure. Mn exposure is associated with many types of diseases, and the most concerned is neurological disorders. In its final stage, Mn toxicity manifests as a neurological disorder termed manganism, which closely resembles Parkinson's disease. The symptoms of chronic Mn toxicity, once established, become progressive and irreversible. Hence, a biomarker for the assessment of cumulative Mn exposure and early diagnosis of Mn neurotoxicity is crucial. In this project, a potential valuable biomarker for long term cumulative Mn exposure will be tested among a well-established workers population with a known history of Mn exposure. This biomarker involves measuring Mn in human bone in vivo. This technology has been developed and validated in the PI's laboratory for the past four years and it's now ready to be tested in a human population. Our central hypothesis to be tested in this proposal is that bone Mn (MnBn) is a reliable biomarker for long- term cumulative Mn exposure assessment and for early diagnosis of Mn neurotoxicity. We will recruit 30 smelters and 30 matched controls from a well-established smelter cohort in China, perform noninvasive MnBn measurement on these subjects, estimate cumulative Mn exposure using an existing exposure model, and establish the relationship between MnBn and estimated cumulative Mn exposure. We will also conduct neurocognitive and neurobehavioral tests on the recruited subjects and determine the relationship between MnBn concentrations and neurobehavioral test scores among the exposed and control groups. At the completion of the project, we will be able to determine whether Mn can be used as a good biomarker for cumulative Mn exposure and for early diagnosis of Mn neuro-toxicity. The use of a new biomarker to understand the neurotoxic effects of exposure to Mn is critical to millions of workers who have been exposed to Mn for two reasons. First, neurological disorder is one of the main health issues for these workers; second, neurological impairment reduces the workers' productivity and is a major cause for work related injuries. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page